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2013 Grants - Weinshenker

Does Alzheimer's Disease Pathogenesis Begin in the Locus Coeruleus?

David Weinshenker, Ph.D.
Emory University
Atlanta, Georgia

2013 Investigator-Initiated Research Grant

The locus coeruleus is a small, specialized region of the brain known to be especially vulnerable to cell death in the early stages of Alzheimer's disease. Nerve cells in the locus coeruleus send long branches to many other parts of the brain; therefore, what happens in the locus coeruleus can affect many other parts of the brain.

Recent studies have found evidence that one of the brain changes characteristic of Alzheimer's disease, the formation of neurofibrillary tangles, may occur in the locus coeruleus before anywhere else. Thais finding has led to the idea that neurofibrillary tangles may start forming in the locus coeruleus and then spread to other parts of the brain by following the long branches of locus coeruleus nerve cells.

David Weinshenker, Ph.D., and colleagues have proposed to test this idea using two different approaches. In the first approach, the researchers will grow nerve cells from the locus coeruleus in laboratory dishes. They will determine if those cells are susceptible to toxicity when exposed to abnormal forms of the protein tau, which is the main constituent of neurofibrillary tangles. For the second approach, Dr. Weinshenker and colleagues will study mice that have been genetically altered to have abnormal tau in the locus coeruleus. Using these mice, they will determine if abnormal tau produced in the locus coeruleus is able to spread to other parts of the brain and cause detrimental changes. These studies will help to clarify some of the earliest steps in the development of Alzheimer's disease in the brain.